A model based on structure-activity relationships of the aspartyl dipeptide sweeteners has been proposed. This model elucidates key factors which are necessary to produce the proper molecular topology involved in the interaction of these tastants with the receptor site. The model describes the tastant as composed of two parts: a polar zwitterionic section which provides the basic for molecular interaction and a hydrophobic section which triggers the sweet taste by inducing a conformational change in key proteins of the receptor site in the taste bud. The flat zwitterionic moiety is restricted in size but not the exact location of the charges; thus aspartyl and aminomethyl malonyl dipeptides are sweet but similar glutamyl dipeptide derivatives are not. The presence and orientation of the peptide bond is important for the proper molecular interaction. Methylation of the peptide bond or replacement of the latter with an ester bond both cause loss of sweetness. The configuration at the asymmetric center of the second residue depends on the size and hydrophobic character of the attached groups. Maximum sweetness can be achieved for L-aspartyl-L-dipeptide esters when a methyl ester is used and the side chain of the second residue has reasonable size (5 or 6 carbons) and hydrophobicity. Similarly, intense sweetness is produced when the second residue is of the D-configuration with a small side chain (e.g., D-alanine) and the ester is a larger hydrophobic group such as cyclohexyl, bornyl or related alcohols.